Acetic Acid → HCID 86665099, compound

HRID 1038812Notes

Reaction equation

HRID 1038812 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][CH:14]([CH:17]=O)[CH2:13][CH2:12]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[F:19][CH:20]([F:23])[CH2:21][NH2:22].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][CH:14]([CH2:17][NH:22][CH2:21][CH:20]([F:23])[F:19])[CH2:13][CH2:12]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 1362742,2-DifluoroethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 86665100HCID 86665100, compound

Product 1

HCID 86665099HCID 86665099, compoundYield 89.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

1-(2-Chlorofuro[3,2-d]pyrimidin-4-yl)piperidine-4-carbaldehyde (0.672 g, 2.53 mmol; Preparation #P.1), 2,2-difluoroethanamine (0.226 g, 2.78 mmol, Matrix), and AcOH (0.217 mL, 3.79 mmol) were combined in DCE (25.3 mL) at rt. After about 10 min of stirring, NaBH(OAc)3 (0.804 g, 3.79 mmol) was added in one portion and the mixture was stirred for about 24 h. The mixture was diluted with DCM (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer extracted with DCM (3×15 mL). The combined organics were then washed with saturated aqueous NaHCO3 (25 mL), brine (25 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (80 g silica gel, 50-100% EtOAc/heptane) to provide N-((1-(2-chlorofuro[3,2-d]pyrimidin-4-yl)piperidin-4-yl)methyl)-2,2-difluoroethanamine (0.748 g, 89%): LC/MS (Table 2, Method c) Rt=1.52 min.; MS m/z: 331, 333 (M+H)+.

Workup

  1. stirringthe mixture was stirred for about 24 h
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with DCM (3×15 mL)
  4. washThe combined organics were then washed with saturated aqueous NaHCO3 (25 mL), brine (25 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (80 g silica gel, 50-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-0fdad192b18b4b0880cd9cc6b79a9c7d
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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